Angiotensin (1−7) prevent heart dysfunction and left ventricular remodeling caused by renal dysfunction in 5/6 nephrectomy mice

Abstract

The renin-angiotensin system (RAS) plays a critical role in chronic renal failure associated with heart failure. In the past few years, angiotensin (Ang) (1-7) have been reported to counteract the effects of angiotensin II (Ang II) and were even considered as a new therapeutical target in RAS. The purposes of this study were to examine whether the Ang (1-7) improves the heart function and remodeling of the left ventricle (LV) in mice with 5/6 nephrectomy (NC). We used a 5/6 nephrectomy to induce significant renal dysfunction in wildtype mice (WT). Twelve weeks after NC, WT showed high blood pressure, significant leftventricular dilation and dysfunction, which were accompanied by cardiomyocyte hypertrophy, diffuse interstitial fibrosis and oxidative damage of cardiomyocytes. Exogenous Ang (1-7) injection improved the heart function and remodeling of LV in mice with 5/6 NC accompanied by a reduction in cardiac interstitial fibrosis, inflammatory cytokine expression and oxidative damage levels of cardiomyocytes, decrease in the profibrotic signaling molecule transforming growth factor (TGF)-b and increase in the collagen degradation signaling molecule matrix metalloproteinase (MMP)-2, -9. However, these beneficial effects did not occur in hydralazine-treated mice. These findings suggest that (1) Exogenous Ang (1-7) injection improve the heart function and remodeling of LV in mice with 5/6 NC. (2) These beneficial effects are independent of its anti-blood pressure effect.

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

“…Accordingly, He et al (2004), and later on many other investigators (Iwata et al, 2005;Tallant et al, 2005;Grobe et al, 2006;Iusuf et al, 2008;Mercure et al, 2008;Li et al, 2009;Giani et al, 2010;Gomes et al, 2010;Pei et al, 2010;Varagic et al, 2010;Iwata et al, 2011;Durik et al, 2012;McCollum et al, 2012;Patel et al, 2012;Zeng et al, 2012;de Almeida et al, 2013), described antiremodeling effects of Ang-(1-7) and of other Mas agonists (AVE 0991/CGEN-856S) (Ferreira et al, 2007;Savergnini et al, 2010). These observations are in line with the deleterious cardiac effects of genetic ablation of Mas in mice (Santos et al, 2006;Gava et al, 2012).…”

“…Most of the data related to Mas and its ligand Ang-(1-7) in the heart have shown cardioprotective effects of Ang-(1-7) (Ferreira et al, 2001(Ferreira et al, , 2007Santos et al, 2004;Iwata et al, 2005Iwata et al, , 2011Tallant et al, 2005;Grobe et al, 2006;Iusuf et al, 2008;Mercure et al, 2008;Li et al, 2009;Giani et al, 2010;Gomes et al, 2010;Pei et al, 2010;Santiago et al, 2010;Varagic et al, 2010;Marques et al, 2011Marques et al, , 2012Qi et al, 2011;Durik et al, 2012;McCollum et al, 2012;Patel et al, 2012;Zeng et al, 2012;Cunha et al, 2013;de Almeida et al, 2013) with only one exception .…”

Number and function impairment of resident C-Kit+ cardiac stem cells in mice with renal dysfunction caused by 5/6 nephrectomy

“…2 As previously reported, capillary density decreases in the heart of mouse with chronic renal failure, followed by obvious cardiac myocyte hypertrophy and DNA peroxidation injury. 3,4 The underlying mechanisms, however, remain unclear.…”

Upregulation of Angiotensin (1-7)-Mediated Signaling Preserves Endothelial Function Through Reducing Oxidative Stress in Diabetes

“…Ang (1-7) infusion preserves cardiac function, coronary perfusion, and aortic endothelial function in rats with coronary ligation-induced heart failure and in diabetic hypertensive rats (1,28). Ang (1-7) also prevents cardiac remodeling through a direct effect in Ang IIinduced hypertensive mice (32) and in 5/6 nephrectomy mice (24). As a vasodilator, Ang (1-7) directly relaxes several vascular beds (3,41,42).…”